The last 50 years have witnessed significant advances in medical research on the mechanisms of action of cannabis, Progress began in 1964 with the isolation and structural clarification of THC.

T
his allowed for exploration and identification of a receptor, CB1, with which THC interacts, followed by discovery of anandamide, the endogenous cannabinoid corresponding to THC.

Since then, an additional endogenous cannabinoid receptor, CB2, has been identified. And many more cannabinoids, which bind to these receptors including those found in the cannabis plant as well as those produced by the human body, have been discovered.

The two receptors, found throughout the human body, are now accepted as comprising the endocannabinoid system, including the central nervous system (CNS), immune system, gastrointestinal (GI) tract, reproductive system, cardiovascular system, and endocrine network.1

The endocannabinoid system acts to regulate neurotransmitter release at the level of the synapse; it functions in parallel and in conjunction with adrenergic, cholinergic, and dopaminergic systems in both the central and autonomic nervous systems. CB1 receptors reside primarily in the CNS in areas of the brain that control learning, memory, movement, coordination, and responses to stress; they are also widely distributed in the gut. Their presence in the CNS is the reason that cannabis has psychoactive properties. CB2 receptors essentially reside only in the periphery, where their activity is intrinsic to cellular and humoral responses related to neuroinflammation and pain, as well as critical GI functions of digestion and host defense.2

Considering the breadth of distribution of CB1 and CB2 receptors, and the varied results associated with binding of either plant-derived or endogenous cannabinoids to these receptors, the therapeutic potential is clear. They are distributed so widely, however, that activation for one purpose may cause unwanted side effects; thus, there remains much to be done to improve our understanding on how best to capitalize on the benefits of medical cannabis without harm to patients.